Design considerations for the synthesis of polymer coated iron oxide nanoparticles for stem cell labelling and tracking using MRI

Abstract

Iron oxide nanoparticles (IONPs, sometimes called superparamagnetic iron oxide nanoparticles or SPIONs) have already shown promising results for in vivo cell tracking using magnetic resonance imaging (MRI). To fully exploit the potential of these materials as contrast agents, there is still a need for a greater understanding of how they react to physiological conditions. A key aspect is the specific nature of the surface coating, which can affect important properties of the IONPs such as colloidal stability, toxicity, magnetism and labelling efficiency. Polymers are widely used as coatings for IONPs as they can increase colloidal stability in hydrophilic conditions, as well as protect the iron oxide core from degradation. In this tutorial review, we will examine the design and synthesis approaches currently being employed to produce polymer coated IONPs as cell tracking agents, and what considerations must be made. We will also give some perspective on the challenges and limitations that remain for polymer coated IONPs as MRI contrast agents for stem cell tracking.

Evaluating the effectiveness of transferrin receptor‐1 (TfR1) as a magnetic resonance reporter gene

“…With SPION labelling, intracellular iron concentrations of more than 5 pg/cell can easily be achieved 7, 34, and importantly the inherent superparamagnetism of the SPIONs means that, in contrast to FC, MR detection is not reliant on the availability of ferritin.…”

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

“…14,22,23 However, these products are no longer on the market. 12,24 Alternatively, FDAapproved ferumoxytol/Feraheme (AMAG Pharmaceuticals Inc), developed to treat iron deficiency anemia, 25 has been used for MRI, 26 and cell labeling has been achieved after cell incubation with nanocomplexes of ferumoxytol-heparin-protamine. To the best of our knowledge, the most sensitive MRI detection has been accomplished for 1,000 ferumoxytol-labeled cells after intracerebral implantation when cells were labeled with 2.2 pg Fe per cell.…”

“…9,10 In addition, parameters such as cell injection site and dose, cell survival, and cell engraftment require optimization in some disease models. [11][12][13][14][15] For these reasons, monitoring of cell therapies is of high clinical relevance and, despite several challenges to overcome, magnetic resonance imaging (MRI) continues to be the method of choice, offering high tissue penetration depth and spatial resolution in comparison with alternative methods. 16,17 Drawbacks of MRI such as low specificity due to unspecific signal from phagocytosed injected cells, dead cells, or local hemorrhage 14,18,19 have been shown to limit the use of MRI for cell imaging in longitudinal studies, and considerable research efforts are devoted to finding alternative/complementary methods.…”

In vivo fate of free and encapsulated iron oxide nanoparticles after injection of labelled stem cells

“…16 Appropriate MRI contrast agents 17,18 for cell tracking include superparamagnetic iron oxide nanoparticles (SPIONs) which generate a negative contrast. 11,[19][20][21][22][23][24] The uptake efficiency of SPIONs is strongly influenced by their functionalization. 21,25 Recently, positively-charged DEAE (diethylaminoethyl)-dextran coated SPIONs have been synthesized for enhanced cellular uptake and MRI contrast.…”

“…11,[19][20][21][22][23][24] The uptake efficiency of SPIONs is strongly influenced by their functionalization. 21,25 Recently, positively-charged DEAE (diethylaminoethyl)-dextran coated SPIONs have been synthesized for enhanced cellular uptake and MRI contrast. 20,22 Upon cell uptake, the clustering and confinement of these particles in endosomal and lysosomal compartments affects their abilities to alter the relaxation rate and hence relaxivity of the surrounding water molecules.…”